EIN2-directed translational regulation of ethylene signaling in Arabidopsis.

Ethylene is a gaseous phytohormone that plays vital roles in plant growth and development. Previous studies uncovered EIN2 as an essential signal transducer linking ethylene perception on ER to transcriptional regulation in the nucleus through a "cleave and shuttle" model. In this study, we report another mechanism of EIN2-mediated ethylene signaling, whereby EIN2 imposes the translational repression of EBF1 and EBF2 mRNA. We find that the EBF1/2 3' UTRs mediate EIN2-directed translational repression and identify multiple poly-uridylates (PolyU) motifs as functional cis elements of 3' UTRs. Furthermore, we demonstrate that ethylene induces EIN2 to associate with 3' UTRs and target EBF1/2 mRNA to cytoplasmic processing-body (P-body) through interacting with multiple P-body factors, including EIN5 and PABs. Our study illustrates translational regulation as a key step in ethylene signaling and presents mRNA 3' UTR functioning as a "signal transducer" to sense and relay cellular signaling in plants. VIDEO ABSTRACT.

HBI transcription factor-mediated ROS homeostasis regulates nitrate signal transduction.

Nitrate is both an important nutrient and a critical signaling molecule that regulates plant metabolism, growth, and development. Although several components of the nitrate signaling pathway have been identified, the molecular mechanism of nitrate signaling remains unclear. Here, we showed that the growth-related transcription factors HOMOLOG OF BRASSINOSTEROID ENHANCED EXPRESSION2 INTERACTING WITH IBH1 (HBI1) and its three closest homologs (HBIs) positively regulate nitrate signaling in Arabidopsis thaliana. HBI1 is rapidly induced by nitrate through NLP6 and NLP7, which are master regulators of nitrate signaling. Mutations in HBIs result in the reduced effects of nitrate on plant growth and ∼22% nitrate-responsive genes no longer to be regulated by nitrate. HBIs increase the expression levels of a set of antioxidant genes to reduce the accumulation of reactive oxygen species (ROS) in plants. Nitrate treatment induces the nuclear localization of NLP7, whereas such promoting effects of nitrate are significantly impaired in the hbi-q and cat2 cat3 mutants, which accumulate high levels of H2O2. These results demonstrate that HBI-mediated ROS homeostasis regulates nitrate signal transduction through modulating the nucleocytoplasmic shuttling of NLP7. Overall, our findings reveal that nitrate treatment reduces the accumulation of H2O2, and H2O2 inhibits nitrate signaling, thereby forming a feedback regulatory loop to regulate plant growth and development.

Exosomes derived from cancer-associated fibroblasts promote tumorigenesis, metastasis and chemoresistance of colorectal cancer by upregulating circ_0067557 to target Lin28.

BACKGROUND: Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression. METHODS: Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay. RESULTS: Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors. CONCLUSION: Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.

Selective Synthesis of Amides and α-Ketoamides via Electrochemical Decarboxylation and Dehydration.

An electrochemical and selective decarboxylation and dehydration using α-keto acids with amines is accomplished, which leads to the easy accessibility of amides and α-ketoamides, which are not only ubiquitous and valuable structure motifs found in pharmaceuticals, but also versatile building blocks in synthetic chemistry. Notably, for this efficient and green protocol, neither metal catalysts nor external oxidants are required. The process exhibits a broad scope and functional group tolerance to deliver various amides and α-ketoamides. Moreover, these two reactions have also been applied to late-stage derivatization and can be safely conducted on gram scale.

Extraction of Moso Bamboo Parameters Based on the Combination of ALS and TLS Point Cloud Data.

Extracting moso bamboo parameters from single-source point cloud data has limitations. In this article, a new approach for extracting moso bamboo parameters using airborne laser scanning (ALS) and terrestrial laser scanning (TLS) point cloud data is proposed. Using the field-surveyed coordinates of plot corner points and the Iterative Closest Point (ICP) algorithm, the ALS and TLS point clouds were aligned. Considering the difference in point distribution of ALS, TLS, and the merged point cloud, individual bamboo plants were segmented from the ALS point cloud using the point cloud segmentation (PCS) algorithm, and individual bamboo plants were segmented from the TLS and the merged point cloud using the comparative shortest-path (CSP) method. The cylinder fitting method was used to estimate the diameter at breast height (DBH) of the segmented bamboo plants. The accuracy was calculated by comparing the bamboo parameter values extracted by the above methods with reference data in three sample plots. The comparison results showed that by using the merged data, the detection rate of moso bamboo plants could reach up to 97.30%; the R2 of the estimated bamboo height was increased to above 0.96, and the root mean square error (RMSE) decreased from 1.14 m at most to a range of 0.35-0.48 m, while the R2 of the DBH fit was increased to a range of 0.97-0.99, and the RMSE decreased from 0.004 m at most to a range of 0.001-0.003 m. The accuracy of moso bamboo parameter extraction was significantly improved by using the merged point cloud data.

The Neglected Role of Asphaltene in the Synthesis of Mesophase Pitch.

This study investigates the synthesis of mesophase pitch using low-cost fluid catalytic cracking (FCC) slurry and waste fluid asphaltene (WFA) as raw materials through the co-carbonization method. The resulting mesophase pitch product and its formation mechanism were thoroughly analyzed. Various characterization techniques, including polarizing microscopy, softening point measurement, Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA), were employed to characterize and analyze the properties and structure of the mesophase pitch. The experimental results demonstrate that the optimal optical texture of the mesophase product is achieved under specific reaction conditions, including a temperature of 420 °C, pressure of 1 MPa, reaction time of 6 h, and the addition of 2% asphaltene. It was observed that a small amount of asphaltene contributes to the formation of mesophase pitch spheres, facilitating the development of the mesophase. However, excessive content of asphaltene may cover the surface of the mesophase spheres, impeding the contact between them and consequently compromising the optical texture of the mesophase pitch product. Furthermore, the inclusion of asphaltene promotes polymerization reactions in the system, leading to an increase in the average molecular weight of the mesophase pitch. Notably, when the amount of asphaltene added is 2%, the mesophase pitch demonstrates the lowest ID/IG value, indicating superior molecular orientation and larger graphite-like microcrystals. Additionally, researchers found that at this asphaltene concentration, the mesophase pitch exhibits the highest degree of order, as evidenced by the maximum diffraction angle (2θ) and stacking height (Lc) values, and the minimum d002 value. Moreover, the addition of asphaltene enhances the yield and aromaticity of the mesophase pitch and significantly improves the thermal stability of the resulting product.

Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers.

Mesenchymal gastrointestinal cancers are represented by the gastrointestinal stromal tumors (GISTs) which occur throughout the whole gastrointestinal tract, and affect human health and economy globally. Curative surgical resections and tyrosine kinase inhibitors (TKIs) are the main managements for localized GISTs and recurrent/metastatic GISTs, respectively. Despite multi-lines of TKIs treatments prolonged the survival time of recurrent/metastatic GISTs by delaying the relapse and metastasis of the tumor, drug resistance developed quickly and inevitably, and became the huge obstacle for stopping disease progression. Immunotherapy, which is typically represented by immune checkpoint inhibitors (ICIs), has achieved great success in several solid tumors by reactivating the host immune system, and been proposed as an alternative choice for GIST treatment. Substantial efforts have been devoted to the research of immunology and immunotherapy for GIST, and great achievements have been made. Generally, the intratumoral immune cell level and the immune-related gene expressions are influenced by metastasis status, anatomical locations, driver gene mutations of the tumor, and modulated by imatinib therapy. Systemic inflammatory biomarkers are regarded as prognostic indicators of GIST and closely associated with its clinicopathological features. The efficacy of immunotherapy strategies for GIST has been widely explored in pre-clinical cell and mouse models and clinical experiments in human, and some patients did benefit from ICIs. This review comprehensively summarizes the up-to-date advancements of immunology, immunotherapy and research models for GIST, and provides new insights and perspectives for future studies.

Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells.

The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples.

Attosecond-precision balanced timing detector with a single photodiode.

We experimentally demonstrate a novel and practical timing detector based on a double-pass acousto-optic frequency shifter. With time and frequency multiplexing, for the first time to our knowledge, a balanced detection is realized using only a single photodiode, which greatly decreases the excess electronic noise during photodetection. With a total input optical power of 1.4 mW (0.35 mW per pulse train), an almost shot-noise-limited detection floor of 28.3 zs/√Hz is achieved, and the timing jitter integrated from 1 kHz to 1 MHz is reduced from 99.0 as (without eliminating the photodetector electronic noise) to only 30.4 as. Even with an input power of 50 µW per pulse train, 221.4 zs/√Hz detection floor and 268.0 as integrated timing jitter at [1 kHz and 1 MHz] are still maintained. This timing detector provides a powerful tool for high-precision metrology, ultra-long-distance ranging, and large-scale timing synchronization.

Electrochemical N-Acylation of Sulfoximine with Hydroxamic Acid.

Despite the widespread applications of sulfoximines, green and efficient access to functionalized sulfoximines remains a challenge. By employing an electrochemical strategy, we describe an approach for the construction of N-aroylsulfoximines, which features a broad substrate scope, mild reaction conditions, safety on a gram scale, and no need for an external oxidant and transition metal catalysts.

Selective Electrochemical Halogenation of Functionalized Quinolone.

This work describes an effective C3-H halogenation of quinoline-4(1H)-ones under electrochemical conditions, in which potassium halides serve as both halogenating agents and electrolytes. The protocol provides expedient access to different halogenated quinoline-4(1H)-ones with unique regioselectivity, broad substrate scope, and gram-scale synthesis employing convenient, environmentally friendly electrolysis, in an undivided cell. Mechanism studies have shown that halogen radicals can promote the activation of N-H bonds in quinolones.

Camera spatial arrangement influence on reconstruction accuracy of chemiluminescence tomography.

Computed tomography of chemiluminescence (CTC) has been demonstrated to be a powerful tool for three-dimensional (3D) combustion visualization and measurement, in which the number of cameras and their spatial arrangement significantly impact the tomographic reconstruction quality. In this work, the relationship of the camera spatial arrangement and tomographic reconstruction accuracy is theoretically established based on two-dimensional (2D) and 3D Mojette transforms and their accurate reconstruction conditions. Numerical simulations and experiments were conducted to demonstrate the theories. The results suggest that the exact reconstruction conditions of the Mojette transforms can be used to determine the minimum number of cameras required for tomography reconstruction, and its achieved reliability can be used as an indicator to predict the reconstruction quality. Besides, the 2D coplanar semicircular configuration exhibits a better performance than that of the 3D non-coplanar arrangement. When the 3D non-coplanar arrangement is adopted, the cameras should be widely distributed in the hemispherical space. The related research provides a theoretical basis for the establishment of the CTC system and other tomography modalities.

Spontaneous outflow efficiency of confined liquid in hydrophobic nanopores.

The suspension of nanoporous particles in a nonwetting liquid provides a unique solution to the crux of superfluid, sensing, and energy conversion, yet is challenged by the incomplete outflow of intruded liquid out of nanopores for the system reusability. We report that a continuous and spontaneous liquid outflow from hydrophobic nanopores with high and stable efficiency can be achieved by regulating the confinement of solid-liquid interactions with functionalized nanopores or/and liquids. Full-scale molecular-dynamics simulations reveal that the grafted silyl chains on nanopore wall surfaces will promote the hydrophobic confinement of liquid molecules and facilitate the molecular outflow; by contrast, the introduction of ions in the liquid weakens the hydrophobic confinement and congests the molecular outflow. Both one-step and multistep well-designed quasistatic compression experiments on a series of nanopores/nonwetting liquid material systems have been performed, and the results confirm the outflow mechanism in remarkable agreement with simulations. This study offers a fundamental understanding of the outflow of confined liquid from hydrophobic nanopores, potentially useful for devising emerging nanoporous-liquid functional systems with reliable and robust reusability.

Sinkhole Attack Defense Strategy Integrating SPA and Jaya Algorithms in Wireless Sensor Networks.

A sinkhole attack is characterized by low difficulty to launch, high destructive power, and difficulty to detect and defend. It is a common attack mode for wireless sensor networks. This paper proposes a sinkhole attack detection and defense strategy integrating SPA and Jaya algorithms in wireless sensor networks (WSNs). Then, combined with the SPA trust model, the trust values of suspicious nodes were calculated, and the attack nodes were detected. The Jaya algorithm was adopted to avoid the attacked area so that nodes can find the route to communicate with the real Sink, and attack nodes are isolated in the network to improve the capabilities of network directional defense. The simulation results show that the improved detection algorithm can effectively detect malicious nodes in the network, and the defense strategy implemented in the attacked area can improve the packet delivery rate, reduce network delay and energy consumption, and improve the security and reliability of wireless sensor networks.

Treadmill exercise promotes E3 ubiquitin ligase to remove amyloid ß and P-tau and improve cognitive ability in APP/PS1 transgenic mice.

BACKGROUND: Moderate physical exercise is conducive to the brains of healthy humans and AD patients. Previous reports have suggested that treadmill exercise plays an anti-AD role and improves cognitive ability by promoting amyloid clearance, inhibiting neuronal apoptosis, reducing oxidative stress level, alleviating brain inflammation, and promoting autophagy-lysosome pathway in AD mice. However, few studies have explored the relationships between the ubiquitin-proteasome system and proper exercise in AD. The current study was intended to investigate the mechanism by which the exercise-regulated E3 ubiquitin ligase improves AD. METHODS: Both wild type and APP/PS1 transgenic mice were divided into sedentary (WTC and ADC) and exercise (WTE and ADE) groups (n = 12 for each group). WTE and ADE mice were subjected to treadmill exercise of 12 weeks in order to assess the effect of treadmill running on learning and memory ability, Aß plaque burden, hyperphosphorylated Tau protein and E3 ubiquitin ligase. RESULTS: The results indicated that exercise restored learning and memory ability, reduced Aß plaque areas, inhibited the hyperphosphorylation of Tau protein activated PI3K/Akt/Hsp70 signaling pathway, and improved the function of the ubiquitin-proteasome system (increased UCHL-1 and CHIP levels, decreased BACE1 levels) in APP/PS1 transgenic mice. CONCLUSIONS: These findings suggest that exercise may promote the E3 ubiquitin ligase to clear ß-amyloid and hyperphosphorylated Tau by activating the PI3K/Akt signaling pathway in the hippocampus of AD mice, which is efficient in ameliorating pathological phenotypes and improving learning and memory ability.

Domestication-associated PHYTOCHROME C is a flowering time repressor and a key factor determining Setaria as a short-day plant.

Phytochromes play vital roles in the regulation of flowering time, but little is known in Panicoideae species, especially the C4 model Setaria. Here, genomic variations of PHYTOCHROME C (PHYC) between wild and cultivated Setaria gene pools were analysed and three SiphyC mutants were identified. The function of SiPHYC was verified by CRISPR-Cas9 approach and transcriptome sequencing. Furthermore, efficiency of indoor cultivation of SiphyC mutants were systematically evaluated. An extreme purified selection of PHYC was detected in wild to cultivated domestication process of Setaria. SiphyC mutants and knockout transgenic plants showed an early heading date and a loss of response to short-day photoperiod. Furthermore, variable expression of SiFTa, SiMADS14 and SiMADS15 might be responsible for promoting flowering of SiphyC mutants. Moreover, SiphyC mutant was four times that of the indoor plot ratio of wild-type and produced over 200 seeds within 45 d per individual. Our results suggest that domestication-associated SiPHYC repressed flowering and determined Setaria as a short-day plant, and SiphyC mutants possess the potential for creating efficient indoor cultivation system suitable for research on Setaria as a model, and either for maize or sorghum as well.

LINC00261 relieves the progression of sepsis-induced acute kidney injury by inhibiting NF-κB activation through targeting the miR-654-5p/SOCS3 axis.

Sepsis is a life-threatening disease, which can cause the dysfunction of multiple organs, including kidney. Recently, a number of studies found that the long non-coding RNA (lncRNA) is closely associated with the development and progression of sepsis; however, the role of long intergenic non-protein coding RNA 261 (LINC00261) in sepsis-induced acute kidney injury is poorly understood. In this study, we found the expression of LINC00261 was significantly decreased in the serum of patients with sepsis than healthy controls. A similar result was also observed in the mouse model of sepsis induced by lipopolysaccharide (LPS). Further investigations revealed that overexpression of LINC00261 improved the viability, suppressed the apoptosis and reduced the generation of inflammatory cytokines in LPS-treated HK-2 cells. Mechanistically, we confirmed that LINC00261 could function as a sponge to combine with microRNA-654-5p (miR-654-5p) which inhibits nuclear factor-κB (NF-κB) activity by targeting suppressor of cytokine signaling 3 (SOCS3). In conclusion, our results demonstrate that LINC00261 may regulate the progression of sepsis-induced acute kidney injury via the miR-654-5p/SOCS3/NF-κB pathway and therefore provides a new insight into the treatment of this disease.

Genome-Directed Discovery of Tetrahydroisoquinolines from Deep-Sea Derived Streptomyces niveus SCSIO 3406.

A genome-directed discovery strategy to identify new tetrahydroisoquinolines (THIQs) was applied to deep-sea derived Streptomyces niveus SCSIO 3406; 11 THIQs were found representing three THIQ classes. Known aclidinomycins A (1) and B (2) were isolated along with nine new compounds, aclidinomycins C-K (3-11). The structures were elucidated using extensive spectroscopic analyses and single-crystal X-ray diffraction methods. The core skeleton of compounds 6-9 contains a fused tetrahydropyran (THP) as an integral part of a distinct type of 6/6/6/6/5/5 polycyclic motif. This is the first report of such a system. Beyond their discovery, we also report here a proposed biosynthetic route to these interesting natural products as well as a preliminary survey of their antimicrobial activities.

High mobility group AT-hook 2 promotes tumorigenicity of pancreatic cancer cells via upregulating ANLN.

HMGA2 is associated with the regulation of cellular biological processes in various human disorders and cancer progression, yet little is known about how HMGA2 controls tumorigenesis. This study uncovered the mechanism of HMGA2-mediated regulation of tumorigenicity in pancreatic cancer. We showed that HMGA2 was highly expressed in pancreatic cancer cells and correlated with poor prognosis. HMGA2 expression knockdown inhibited the tumorigenicity of pancreatic cancer cells. Conversely, overexpression of HMGA2 promoted tumorigenicity. Combination of ChIP-Seq, RNA-Seq and dual-luciferase reporter assays revealed HMGA2 could directly regulate ANLN expression. Furthermore, we found ANLN could mediate the HMGA2-induced effects on pancreatic cancer cells. The identification of the regulatory mechanism of HMGA2 and ANLN will provide insights into the progression for human pancreatic cancer.

Exact reconstruction condition for angle-limited computed tomography of chemiluminescence.

Computed tomography of chemiluminescence (CTC) is an effective technique for three-dimensional (3D) combustion diagnostics. It reconstructs the 3D concentrations of intermediate species or 3D images of flame topology by multiple chemiluminescence projections captured from different perspectives. In the previous studies of CTC systems, it was assumed that projections from arbitrary perspectives are available. However, for some practical applications, the range of view angles and the number of projections might be restricted due to the optical access limitation, greatly affecting the reconstruction quality. In this paper, the exact reconstruction condition for angle-limited computed tomography of chemiluminescence was studied based on Mojette transform theories, and it was demonstrated by numerical simulations and experiments. The studies indicate that the object tested within limited angles can be well reconstructed when the number of grids, the number of projections, and the sampling rate of projections satisfy the exact reconstruction condition. By increasing the sampling rate of projections, high-quality tomographic reconstruction can be achieved by a few projections in a small angle range. Although this technique is discussed under combustion diagnostics, it can also be used and adapted for other tomography methods.